Endocrine‐based treatments in clinically‐relevant subgroups of hormone receptor‐positive/her2‐negative metastatic breast cancer: Systematic review and meta‐analysis

Francesco Schettini, Mario Giuliano, Fabiola Giudici, Benedetta Conte, Pietro De Placido, Sergio Venturini, Carla Rognoni, Angelo Di Leo, Mariavittoria Locci, Guy Jerusalem, Lucia Del Mastro, Fabio Puglisi, Pierfranco Conte, Michelino De Laurentiis, Lajos Pusztai, Mothaffar F. Rimawi, Rachel Schiff, Grazia Arpino, Sabino De Placido, Aleix PratDaniele Generali

Research output: Contribution to journalReview articlepeer-review

Abstract

A precise assessment of the efficacy of first‐/second‐line endocrine therapies (ET) ± target therapies (TT) in clinically‐relevant subgroups of hormone receptor‐positive (HR+)/HER2‐negative metastatic breast cancer (MBC) has not yet been conducted. To improve our current knowledge and support clinical decision‐making, we thus conducted a systematic literature search to identify all first‐/second‐line phase II/III randomized clinical trials (RCT) of currently approved or most promising ET ± TT. Then, we performed a meta‐analysis to assess progression‐free (PFS) and/or overall survival (OS) benefit in several clinically‐relevant prespecified subgroups. Thirty‐five RCT were included (17,595 patients). Pooled results show significant reductions in the risk of relapse or death of 26–41% and 12–27%, respectively, depending on the clinical subgroup. Combination strategies proved to be more effective than single‐agent ET (PFS hazard ratio (HR) range for combinations: 0.60–0.65 vs. HR range for single agent ET: 0.59–1.37; OS HR range for combinations: 0.74–0.87 vs. HR range for single agent ET: 0.68–0.98), with CDK4/6‐inhibitors(i) + ET being the most effective regimen. Single agent ET showed comparable efficacy with ET+TT combinations in non-visceral (p = 0.63) and endocrine sensitive disease (p = 0.79), while mTORi‐based combinations proved to be a valid therapeutic option in endocrine‐resistant tumors, as well as PI3Ki + ET in PIK3CA‐mutant tumors. These results strengthen international treatment guidelines and can aid therapeutic decision‐making.

Original languageEnglish
Pages (from-to)1458
Number of pages21
JournalCancers
Volume13
Issue number6
DOIs
Publication statusPublished - Mar 2 2021

Keywords

  • Endocrine therapy
  • Hormone receptor
  • Metastatic breast cancer
  • Meta‐analysis
  • Systematic review

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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